Astragalin (AG), a flavonoid from many traditional herbs and medicinal plants, has been described to exhibit in vitro anti-inflammatory activity. The paper aimed to study the effects of astragalin on anti-inflammatory, anti-oxidative ability and apoptosis signaling pathway in brain tissue of rats with cerebral ischemia-reperfusion injury, and to explore its possible mechanism.astragalin treatment I / R group . After 24 h of reperfusion, the neurological deficits of the rats were analyzed and HE staining was performed. The volume of cerebral infarction was calculated by triphenyltetrazolium chloride (TTC) staining, and the apoptosis of nerve cells was detected by TUNEL staining. In addition, the content of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), glutathione (GSH) assay and glutathione peroxidase (GSH-Px) were measured in rat brain tissue. Western blot analysis was used to determine the expression of related proteins.The rat model of focal cerebral ischemia-reperfusion injury was established by suture method. It was randomly divided into 5 groups, sham operation group, ischemia-reperfusion (I/R) treatment group, and astragalin treatment group. In the astragalin treatment group, MDA and NO levels in I/R rats were reduced, antioxidant enzymes and superoxide dismutase (SOD) activity were increased. In the astragalin treatment group, NF-κB (p65) and cyclooxygenase-2 (COX-2) expression levels were down-regulated, NF-E2-related factor 2 (Nrf2) nucleus and heme oxygenase-1 (HO-1) protein expression levels were up-regulated. In addition, the astragalin treatment can inhibit apoptosis, down-regulate Bax and cleaved caspase-3 expression, up-regulate Bcl-Xl expression.Compared with I/R group, the neurological deficit score and infarct volume of I/R rats were reduced in the astragalin may play an important role in improving cerebral ischemia-reperfusion injury.The antioxidant properties of  Cerebrovascular disease has become one of the three major causes of death in humans, with high morbidity, mortality and disability , 2. CereBrain I/R injury is a complex pathophysiological process. Brain blood flow interruption and reperfusion damage the brain cells is a rapid cascade reaction , 13. ThiAstragalin is the monomer of astragaloside, which is a plant monomer of saponins isolated from Astragalus membranaceus and the main effective component of Astragalus membranaceus [astragalin. A large number of studies have shown that astragalin can significantly dilate blood vessels, improve microcirculation and improve heart and cerebral ischemia reperfusion injury [astragalin has not been fully revealed. Therefore, based on the animal model of cerebral ischemia-reperfusion, whether astragalin can alleviate cerebral ischemia-reperfusion injury by improving the antioxidant and anti-inflammatory activities of rats and inhibiting apoptosis pathway was further studied. This study will provide a new research direction of new drugs for the treatment of cerebral ischemia injury.ranaceus , 18. It ranaceus , 20. In n injury . HoweverHealthy male Sprague-Dawley rats, 7–8 weeks old, weighing 200–220 g, a total of 50 were provided by the Experimental Animal Center of China Second Affiliated Hospital of Army Medical University. They were free access to drinking water at room temperature 20–25 °C. All experiments were approved by the Second Affiliated Hospital of Army Medical University Animal Care and Use Committee and conducted in accordance with the National Institutes of Health Laboratory Animal Care and Use Guidelines.astragalin group . The dose of astragalin was chosen based on the results of our pilot experiments. Astragalin was dissolved in 0.1% dimethyl sulfoxide (DMSO) in 1% hydroxyethyl cellulose. At the beginning of brain reperfusion, the animals (except for the sham group and the I/R group) were injected with astragalin immediately by intraperitoneal administration. The murine middle cerebral artery occlusion (MCAO) induced ischemia reperfusion model was prepared following the methods described previously [After 1 week of adaptive feeding, the rats were in good condition and were divided into sham operation group (Sham group), model group (I/R group) and eviously . BrieflyThe brain tissue was stained with 2,3,5-triphenyltetrazolium chloride (TTC) dye for 30 min. The staining results showed that white was infarct focus and red was normal brain tissue. After taking pictures, the area of cerebral infarction was measured by literature method.After 24 h of cerebral ischemia-reperfusion in rats, neurological deficits were scored according to the 5-point standard established in the literature .Five hours after MCAO, the rats were sacrificed by decapitation. Brain tissue sections were embedded and TUNEL staining was performed using a TUNEL assay kit. Computer image analysis  was used to determine the number of apoptotic cells (N) and the positive apoptosis index  of each statistical field.After deep anesthesia, the rats were perfused with normal saline and 40 g/L paraformaldehyde fixative, and stored in 200 g/L sucrose overnight. Coronal sections of 30 μm brain tissue were made by frozen section machine at 2 mm after optic chiasm, and 10–15 μm sections of adjacent tissues were made for HE staining.Five hours after MCAO, the rats were sacrificed by decapitation. The blood was centrifuged for 15 min at 2500 r/ min at 4 °C. The supernatant was absorbed into the centrifugal tube and refrigerated at 4 °C for testing. The right hemisphere was cut from frontal pole to occipital lobe, and the occipital lobe was homogenized in frozen saline. The contents of NO (Griess method), SOD (enzyme labeling method), MDA (thiobarbituric acid method), GSH (colorimetric method) and GSH-Px (colorimetric method) in brain tissue and serum were determined.After 24 h of reperfusion, the rat brain was removed and stored at − 80 °C until use. The supernatant was collected by centrifugation of the brain tissue, total tissue protein was extracted. The protein concentration was quantified using a BCA Protein As-say Kit. After that, it was transferred to the PVDF membrane by electrophoresis. Then anti-Bax (1:1000), Bcl-XL (1:1000), caspase-3 (1:1000), Nrf2 (1:1000), HO-1 (1:1000), p65 (1:1000), COX2 (1:1000) and GAPDH (1:1000) , USA) were added and incubated overnight. 1:5000 labeled anti-rabbit secondary antibody was added for 1 h. After that, the gray values of the target bands and the internal reference bands were recorded by ECL chemiluminescence. The gray ratio of the target bands to the internal reference bands was the relative expression of the target proteins.P < 0.05 indicated that the difference was statistically significant.The monitoring data were analyzed by SPSS19.0 statistical software. The data analysis results were expressed as mean ± standard deviation (mean ± SD). The data analysis between the two groups was performed by t test. The data analysis between multiple groups was based on one-way ANOVA. The LSD test was used as subsequent analysis, astragalin on I/R injury, neurological deficits were scored 24 h after reperfusion. The results were shown in Fig. P < 0.01). The neurological deficit scores of the rats in the astragalin group were significantly decreased in a dose-dependent manner compared with the I / R group .In order to investigate the neuroprotective effects of P < 0.01). Compared with the I/R group, the percentage of infarct size in the dose group of astragalin was dose-dependent  .The results of cerebral infarction area showed a significant increase in the percentage of infarct volume in the I/R group compared with that in the sham group P < 0.0. CompareP < 0.01). The morphology of pyramidal cells in the hippocampus of different doses of astragalin was more regular and more precise. Compared with the I/R group, the number of hippocampal neurons in the astragalin treated group was increased significantly in a dose-dependent manner.The neuroprotective effect of jaundice was analyzed by HE staining. The results were shown in Fig. P < 0.01). The MDA level of the rats in the astragalin group was significantly decreased in a dose-dependent manner compared with that in the I/R group .From the results of Fig. P < 0.01), while astragalin (25 mg/kg and 50 mg/Kg) significantly inhibited the expression of NF-κB (p65) and COX-2 (P < 0.01). In addition, analysis of NO levels in rat brain showed a significant increase in NO levels in the I/R group compared with that in the sham group (P < 0.01). Different doses of astragalin significantly reduced NO levels in a dose-dependent manner   Fig. d.Fig. 4astragalin on nuclear translocation of Nrf2, protein expression of HO-1 and antioxidant enzyme activity were analyzed in I/R rats. The results were shown in Fig. P < 0.01). The expression of Nrf2/Lamin B1 and HO-1 protein in nucleus of cells treated with different doses of astragalin was significantly increased . The results indicated that astragalin can increase the antioxidant defense ability in tissues. The SOD, GSH and GSH-Px in the nucleus of the I / R group were significantly lower than that in the sham group (P < 0.01), while the levels of SOD, GSH and GSH-Px were significantly increased in the different doses of astragalin treatment group  . Compared with the I/R group, the number of TUNEL -positive cells in the ischemic penumbra was significantly reduced in a dose-dependent manner after treatment with different doses of astragalin .TUNEL staining was performed to clarify whether the neuroprotective effects of sis Fig. . A smallastragalin are related to the anti-apoptotic pathway, the expression of Bcl-Xl, Bax and c-caspase-3 was analyzed by Western blot. The results showed that compared with sham group, the expression of Bax and c-caspase-3 was significantly increased and the expression of Bcl-Xl was significantly decreased in the I / R group (P < 0.01). Compared with the I/R group, the expression levels of Bax and cleaved caspase-3 were significantly decreased after treatment with different doses of astragalin, and the level of Bcl-Xl protein was significantly increased in a dose-dependent manner   Fig. . These rStroke is an acute cerebrovascular disease caused by a blood supply disorder in the brain , 25 . WhAstragalin is a monomer component of xanthine saponin and is the main active ingredient in the preparation of astragalin [astragalin has a certain effect on promoting the recovery of the body and improving the prognosis. It can improve the immunity of the body, promote the excretion of oxygen free radicals, improve microcirculation, and resist lipid peroxidation [astragalin can alleviate cerebral ischemia-reperfusion injury in rats [astragalin has not been fully elucidated. In this study, a rat model of cerebral ischemia-reperfusion was established, which confirmed that astragalin can reduce the neurological damage of cerebral ischemia and the volume of cerebral infarction. It indicated that astragalin had neuroprotective effect on cerebral ischemia in rats.At present, the research on cerebral ischemia-reperfusion injury not only explores the pathophysiological mechanism, but also seeks for effective neuroprotective agents against cerebral ischemia-reperfusion injury, so as to save the life of patients with cerebral ischemia is an important aspect of the treatment of ischemic neurological diseases , 30. Asttragalin . A largexidation . Previou in rats . Despiteastragalin can significantly inhibit the decrease of SOD, CAT and GSH-Px and the increase of MDA in the brain tissue of model rats, indicating that astragalin can reduce the production of free radicals and reduce lipid peroxidation.Studies have shown that oxidative stress is one of the most important pathological mechanisms of ischemic stroke . Oxidatiastragalin was further investigated. The body has produced many defensive mechanisms in the process of anti-oxidative stress, and the activation of Nrf2 / ARE signaling pathway is an important link [astragalin significantly increased the expression of Nrf2 protein in the nucleus and up-regulated the protein expression of HO-1. These results indicated that astragalin may play a neuronal protective role by activating the Nrf2/ARE/HO-1 signaling pathway. However, the molecular mechanism by which Nrf2 was released from the Keap1-Nrf2 complex required subsequent experiments to confirm.The molecular mechanism of the anti-oxidative stress of ant link , 37. It astragalin can significantly reduce the expression of NF-κB p65, indicating that it blocked the activation of NF-κB. As a downstream target gene of NF-κB, COX-2 is rapidly induced to express under cerebral ischemia [astragalin can significantly reduce NO levels and COX-2 expression, and reduce the nerve damage mediated by it.NF-κB normally binds to the inhibitory protein IκB in the form of p65-p50 dimer and is present in the cytoplasm . When thischemia . COX-2 iischemia . Studiesischemia . At the ischemia . The resastragalin, the level of Bcl-Xl protein was significantly increased, and the apoptosis rate was significantly increased. These results indicated that astragalin had protective effect on cerebral ischemia-reperfusion injury. It may be achieved mainly by reducing proapoptotic genes (Bax), caspase-3 and increasing anti-apoptotic genes (Bcl-XL).Numerous studies have shown that excessive neuronal apoptosis after cerebral ischemia is one of the main causes of reperfusion injury and plays an important role in the process of infarction formation . The proAstragalin can protect the brain from brain I / R damage by reducing oxidative stress, inflammation and apoptosis. Therefore, it would provide an experimental basis for the clinical application of astragalin in the treatment of cerebral ischemic diseases, and also provide a theoretical basis for the future development of astragalin.


BackgroundTonsillectomy is one of the most commonly performed surgeries among children. It is indicated for the treatment of obstructive sleep apnea and chronic throat infections. Although a relatively safe surgery, post-operative complications have been reported in multiple studies. Over the past century, tonsillectomy has played a role in post-operative weight gain.AimTo measure weight gain in pediatric patients post-tonsillectomy.Methods2) and weight (kg) of the children were measured, and the BMI (body mass index) was calculated preoperatively and one and six months post-operatively.A retrospective study was conducted in the Al-Ahsa region in Saudi Arabia. Overall, 240 children  from tertiary hospitals were included in the study. The height (mResultsThere were significant differences observed between the mean weight one-month and six months post-operation (P = 0.0001) and the mean BMI measured at the baseline one month and six months post-operation (P = 0.0001). In addition, a positive linear correlation between the BMI six months post-operation and the weight at the same period (R = 0.375) was noted.ConclusionThe findings of this study suggest an increase in weight post-tonsillectomy, mostly six months post-operation. Future studies, however, are warranted to evaluate the risk factors associated with weight gain in children and its relation to tonsillectomy. Tonsillectomy is a commonly performed surgery in pediatric patients . It has Children with recurrent acute tonsillitis suffer from reduced dietary intake. Studies have reported a rapid increase in weight gain post-tonsillectomy in some patients -11. Rece2) and weight (kg) of the children were measured preoperatively and one month and six months post-operatively. Furthermore, the BMI was calculated by dividing weight in kilograms over squared height (m2). The given values were compared to the growth chart of healthy Saudi children by percentiles based on age and gender: underweight (BMI <5th percentile), normal (BMI 5th-85th percentile), overweight (BMI 85th-95th percentile), and obese (BMI ≥95th percentile). The inclusion criteria were Saudi children aged 1 to 15 years who underwent adenotonsillectomy between January 2018 and March 2019 period for the following indications: OSA, recurrent acute tonsillitis, and tonsillar hypertrophy. Children with chronic disease and congenital malformation were excluded from the study. This study was approved by the research committee of King Faisal University, Al-Ahsa, Saudi Arabia.A retrospective study was conducted in the Al-Ahsa region of Saudi Arabia between January 2018 and March 2019. Overall, 240 children aged 1 and 15 years from tertiary hospitals who underwent adenotonsillectomy were included in this study. Informed consent was obtained. Patient’s demographics include age, gender, residency, file number, and date and cause of the surgery. Height . Descriptive statistics were used for quantitative data as the minimum and maximum range as well as the mean±SD for quantitative normally distributed data, while it was used for qualitative data as number and percentage. A correlation test was conducted between gender and BMI measurement. A P-value was 0.05 at a 90% confidence interval to determine the statistical significance.Overall, 240  children participated in this study to detect the change of mean weight pre- and post-tonsillectomy, according to the Saudi growth chart. The demographics of all included cases were as follows: age range, 1-15 years with a mean±SD of 7.45±2.89. The mean±SD of weight pre-operation, one month, and six months postoperation were 30.433±11.6, 30.53±12.05, and 33.25±12.27, respectively. Whereas the mean±SD of height pre-operation, one month, and six months post-operation was 1.14±0.18 m, 1.15±0.18 m, and 1.19±0.18 m. Regarding the BMI, the mean±SD of BMI pre-operation was 22.35±3.98, whereas the mean±SD of BMI one month and six months post-operation was 21.98±4.04 and 22.46±3.69, respectively. The characteristics of the participated children are shown in Table The mean weight pre- and post-operation for both genders are shown in Figure Figure The classification of children according to the percentile growth chart pre- and six months post-tonsillectomy is shown in Figure There was a significant difference between the mean weight one month and six months post-operation (P < 0.0001). A repeated measure ANOVA test to investigate the differences in the weight at the baseline and one month and six months post-operation showed that there was a significant difference in the mean weight (P = 0.0001). There was a significant difference between the BMI measured at the baseline and one month and six months post-operation (P = 0.0001). In addition, there was a significant difference between the mean different percentile growth charts at the baseline and six months post-operation (P < 0.005). The Pearson correlation between the percentile growth chart and gender showed a significant correlation between these two variables (P = 0.034) pre- and post-operation (P < 0.013). Girls comprised the majority of the overweight group, whereas boys comprised the large majority of the obese group.BMI at the baseline and after six months post-tonsillectomy can serve as a predictor for percentile growth chart before and after surgery with a statistically significant correlation (P = 0.000), with a 95% confidence interval Figure . There wIn the present study, we collected and reviewed the data of 240 children who underwent a tonsillectomy at tertiary hospitals. The mean age of the children was 7.45±2.89 years old, with females more dominant than males. The mean weight of children after the surgery of one month increased and after six months increased in boys, whereas it decreased in girls. The mean of the overall weight increased after surgery compared to the weight before surgery; there was a significant difference between the weight at the baseline and after six months of the surgery. Also, there was a significant difference between the weight at baseline, one month, and six months after surgery. Regarding the height, the mean height in this study was increased after the surgery compared to the baseline before the surgery. A case-control study that included 154 children who underwent adenotonsillectomy   demonstAnother suggestion of the variation in the findings can be attributed to the study design. This is a retrospective study, and it only included children who underwent tonsillectomy, with no control group. We compared the increase in weight gain in the same group of children, whereas the other previous studies included a control group using a questionnaire -21, whicThe findings of our study suggest that there is an increase in weight gain post-tonsillectomy. The difference is mostly observed in six months post-operation, with a positive linear correlation between weight and BMI. Further studies are warranted to evaluate the other risk factors associated with weight gain in children and its relation to tonsillectomy.


Post-treatment dose measurement is mainly performed to confirm the planned absorbed dose to the tumor and non-tumor liver volumes. This study compared the predicted and measured absorbed dose distributions.Selective internal radiation therapy (SIRT) is a promising treatment for unresectable hepatic malignancies. Predictive dose calculation based on a simulation using m99Tc-MAA-SPECT and 90Y-TOF-PET imaging. The voxel-level dose distribution was derived using the local deposition model. Liver perfusion territories and tumors have been delineated on contrast-enhanced CBCT images, which have been acquired during the m99Tc-MAA work-up. Several dose-volume histogram (DVH) parameters together with the mean dose for liver perfusion territories and non-tumoral and tumoral compartments were evaluated.Thirty-one patients (67 tumors) treated by SIRT with resin microspheres were analyzed. Predicted and delivered absorbed dose was calculated using r = 0.937). The ratio of measured and predicted mean dose to this volume has a first, second, and third interquartile range of 0.83, 1.05, and 1.25. The difference between the measured and predicted mean dose did not exceed 11 Gy. The correlation between predicted and measured mean dose to the tumor was moderate (r = 0.623) with a mean difference of − 9.3 Gy. The ratio of measured and predicted tumor mean dose had a median of 1.01 with the first and third interquartile ranges of 0.58 and 1.59, respectively. Our results suggest that m99Tc-MAA-based dosimetry could predict under or over dosing of the non-tumoral liver parenchyma for almost all cases. For more than two thirds of the tumors, a predictive absorbed dose correctly indicated either good tumor dose coverage or under-dosing of the tumor.A strong correlation between the predicted and measured mean dose for non-tumoral volume was observed (m99Tc-MAA-based dose estimation to predict non-tumor liver irradiation, which can be applied to prescribe an optimized activity aiming at avoiding liver toxicity. Compared to non-tumoral tissue, a poorer agreement between predicted and measured absorbed dose is observed for tumors.Our results highlight the predictive value of  The reconstruction voxels have a dimension of 2.73 ×2.73×2.79 mm3. For PET/MR system, voxels with 3.13 ×3.13×2.78 mm3 dimensions were smoothed with a Gaussian filter with 7 mm full-width at half-maximum in the x- and y-direction and a  filter in the z-direction.On the day of treatment, for each LPT, the catheter tip was in the same position as during the pre-treatment work-up. A day after administering the prescribed activity, the actual distribution of the microspheres was controlled by a time-of-flight (TOF)-PET examination on either a PET/MR system  or a PET/CT system . The emission data were corrected for randoms, scatter, attenuation, TOF offset, and dead-time, and reconstructed using maximum-likelihood expectation-maximization algorithm using two iterations and 28 subsets. For PET imaging, the standard vendor attenuation correction was used: the attenuation map is estimated from the Dixon MR images  and CT image for the Signa and Discovery systems, respectively. For PET/CT system, a Gaussian post-reconstruction filter of 5 mm full-width at half-maximum in the m99Tc-MAA-SPECT/CT, CBCTs, and post-treatment images are available in Fig. Representative images of All described images in the previous section were imported into the MIM software 6.8.4  for further processing and extracted as DICOM images to be processed in IDL 8.4 . All manual VOI correction/delineation has been done with MIM software, and image processing was performed using in-house software written in IDL.m99Tc-MAA study as well as the CT or MR from the 90Y-PET images. This algorithm is described in detail in our previous publication  for m99Tc-MAA-SPECT voxels and 2.3061×10−3 and 1.7607×10−3 for 90Y-PET voxels form post-treatment PET/CT and PET/MR studies, respectively [Afterward, a map of absorbed dose in Gy was determined using the local deposition model by employing a conversion factor of:ectively .VOI mean dosenth percentile dose, i.e., n% of the volume received a dose of Dn or more ,Dn: d Gy Vd: volume percentage that receives at least Dose-volume histograms (DVHs) for all VOIs were obtained, and also, the mean dose to each VOI was computed. For each liver compartment, a series of clinically relevant dosimetry parameters were compared for predicted and post-treatment measured dose maps:m99Tc-MAA simulation underestimates the tumor dose, but yet the tumor dose is more than these dose thresholds, this underestimation could be less critical than the opposite situation where the pre-treatment simulation suggests a mean dose of more than tumor control threshold, while the post-treatment measured dose is less than the threshold. Using this idea, a scatter plot of predicted and measured tumor dose was partitioned into four areas using 70 Gy as a dose with intermediate tumor response probability. An absorbed dose of 100 Gy is also used to illustrate a high tumor control probability:The derived tumor mean dose for both predictive and post-treatment dose assessments was above 70 Gy: predictive dosimetry suggested a good tumor coverage, which was verified after treatment.Both predicted and post-treatment measured tumor mean dose were below 70 Gy: predictive tumor dosimetry correctly gave an under-treatment warning.Predicted tumor dose was less than 70 Gy, while the measured tumor mean dose reached the 70 Gy criterion: the result of the treatment was better than suggested by the dose prediction.m99Tc-MAA dosimetry falsely predicted a good tumor coverage which did not materialize after treatment.Predicted tumor dose was above 70 Gy while measured tumor mean dose did not reach 70 Gy: In clinical routine, the desired absorbed dose to the tumor is derived from a tumor control probability curve. Using this curve, a minimum threshold of 70 to 100 Gy is widely accepted as a dose with high tumor response probability , 5, 18. The derived NTV mean dose for both predictive dosimetry and dose measurement was below 50 Gy: predictive dosimetry could predict the safety of the treatment for non-tumoral liver parenchyma.Both predicted and post-treatment measured NTV mean dose was above 50 Gy: predictive NTV dosimetry correctly identified a dose range with a non-zero risk for liver complications.Predicted NTV dose was above 50 Gy, while post-treatment measured mean dose to this VOI did not reach 50 Gy: predictive dosimetry falsely suggested a potential risk for liver toxicity.Pre-treatment NTV dose was less than 50 Gy, while measured mean dose of NTV exceeded the 50 Gy limit: pre-treatment dose prediction did underestimate the risk for liver toxicity.The same approach was applied for non-tumoral tissue mean dose using normal tissue complication probability curves. A dose of 50 Gy is considered as a safety threshold. An absorbed dose of 40 Gy is the maximal recommended dose in case of cirrhotic non-tumoral liver tissue or patient heavily treated with chemotherapy , 5:The m99Tc-MAA uptake.For patients whose activity planning was done by employing the partition model, the therapy team agreed on a delivered dose to the non-tumoral liver and tumor compartment, which are called “planned dose criteria” in this document. To calculate the injected activity, the total liver and liver perfusion territories have been drawn on baseline images and tumors have been delineated by thresholding the m99Tc-MAA uptake for tumor definition). Considering post-treatment dose measurement, the difference between planned dose and determined mean dose could be caused by a difference in VOI definition or variation between m99Tc-MAA and therapeutic microspheres distribution. The differences are calculated in a way that negative values show doses below and above the planned dose for NTV and TV compartments, respectively.The planned dose to the NTV and TV was compared to the doses obtained from predictive dosimetry and post-treatment dose measurement using the relative difference between calculated dose and planned dose in percentage. For predictive dosimetry, deviation from zero indicates the effects of the different VOI definition method used in this study (perfusion based LPT and tumor segmentation on CBCTs) compared to activity planning VOI definition  was used for all statistical analysis. A Passing–Bablok regression scatter plot was used to compare dose parameters from predictive and post-treatment dose assessment by displaying the regression line and confidence intervals. This method is commonly used to compare two measurement methods by plotting them in A Bland–Altman plot was also used to calculate the agreement between predicted and post-treatment measured dose parameters. In the Bland–Altman plots, the middle dashed line represents the mean difference, and the purple area is the confidence interval; the green and pink area and their dashed lines also showed the difference ± standard deviation and their confidence intervals to give a visual impression of the precision of these parameters.p value of less than 0.05 was set as a significance threshold.Dose parameters for predictive dose and post-treatment dose measurement were also compared using paired Wilcoxon rank-sum test. A m99Tc-MAA work-up; and in 3 patients, all tumors were smaller than 5 ml and were not considered for dose assessment as partial volume effects are too pronounced. Finally, in the last excluded patient, some voxels within the liver received blood from both administrations within different catheter tip positions in pre-treatment work-up. So, it was not possible to extract fractional uptake for each administration from the m99Tc-MAA-SPECT image.Of 49 consecutive patients identified, 31 patients were included, and 18 patients were excluded see Fig. : in 4 paOf those 31 patients included, 67 tumors (with a volume bigger than 5 ml) in 47 LPTs  were included in this retrospective study. The baseline characteristics for the patients and treatment sessions (LPT) are described in Table n = 1 ; 120 Gy, n = 4; 125 Gy, n = 1; 135 Gy, n = 1; 150 Gy, n = 5; 160 Gy, n = 1; 240 Gy, n = 2; 250 Gy, n = 2; 300 Gy, n = 3) was used. This model also aimed at sparing liver tissue parenchyma from a certain absorbed dose .As detailed in Fig. More details are provided in Table r = 0.990) determined on post- and pre-treatment studies; the ratio of the volumes had a median of 1.01 with a first and third interquartile range of 0.99 and 1.04. These volume differences represented either the volume change during the registration or a real biological change.Considering the 31 patients, there was a high correlation between total liver volumes , this parameter is used to divide the total prescribed vial to be administrated in different branches of the hepatic artery. When comparing this parameter for LPTs defined on CBCTs with the numbers reported on the prescription sheet, the ratio had a median of 0.99 with a wide interquartile range (first and third interquartile range 0.90 and 1.09 respectively) which can directly affect the dosimetric analysis.Two more examples are provided in the supplementary material: (1) an LPT segmentation example on CBCTs, which could be considered superior to a classical liver lobe/segment delineation because of a specific catheterization and (2) an example of lobar treatment (with bilobar work-up) which shows that CBCT-based LPT segmentation nicely followed the activity distribution of the yttrium-90.m99Tc-MAA-SPECT and post-treatment 90Y-PET images were compared for total liver NTV, total LPT, and tumors. Table Absorbed dose distribution parameters of each LPT derived from pre-treatment Two examples of TV, NTV, and total LPT dosimetry are shown in Figs. Sm99Tc-MAA and 90Y distribution has been shown in Table A summary of the tumor dose comparison between r = 0.937). Other reported dose parameters for NTV  also showed a moderate correlation between m99Tc-MAA and 90Y-PET based dosimetry .A Passing–Bablok regression, which has been shown in Fig. Bland–Altman analysis of NTV gave a mean difference of − 0.9 Gy  for mean dose, 0.9 Gy  for D30, and − 0.6%  for V40. The difference between predicted and measured mean dose to the total NTV doses did not exceed 11 Gy.m99Tc-MAA and 90Y distribution. The mean dose of the total LPT estimated on m99Tc-MAA and post-treatment dose measurement were 63.5 and 53.0 Gy. The V30 for pre-treatment dose prediction and post-treatment dose calculations were 49±20 and 46±17 %. For other dosimetric parameters, no significant difference was observed.Table Bland–Altman analysis of LPT see Fig.  gave a mm99Tc-MAA-SPECT and 90Y-PET distributions is shown. Predicted and measured dosimetry showed an average of 152 and 143 Gy mean dose to the tumor. As illustrated in Fig. In Table On average, half of the tumors’ volume received an absorbed dose of 139 and 128 Gy or more based on predictive dosimetry and post-treatment dose measurement; the ratio of measured and pre-treatment predicted D50 has a median of 0.91 (first and third interquartile range of 0.56 and 1.55). Based on analyzing V70, around 65% and 60% of the tumor volumes received more than 70 Gy on predictive and measured dosimetry; these volume portions are reported around 53% and 47% for 100 Gy dose threshold level for predictive and post-treatment dose assessments. Seventy percent of tumor volumes received at least 103±95 Gy using predictive dosimetry while post-treatment dose calculation showed that 70% of the tumor volumes received at least 88±99 Gy; the median, first, and third interquartile ranges of the ratio between D70 in post-treatment dose measurement and predictive dosimetry were 1.05, 0.67, and 1.38 respectively.r = 0.623). On the other hand, our data does not show a significant correlation between other tumor parameters derived from DVH. Bland–Altman analysis of tumors gave a mean difference of − 9.3 Gy  for the mean dose.A Passing–Bablok and Bland–Altman analysis of mean dose to the tumor and D50 and V100 is shown in Fig. In the previous section, pre-treatment dose simulation and post-treatment dose measurement in different VOIs have been compared using mean dose and different DVH parameters.n = 29 and 1 from 31 patients); the blue area represents the patients whose pre-treatment simulation estimates the NTV mean dose of more than 50 Gy, while 90Y-microsphere distribution showed a dose of less than 50 Gy after treatment (n = 1); the red area is the risky area where m99Tc-MAA simulates a safe treatment, whereas the actual dose to a NTV was more than 50 Gy (n = 0). More details are provided in Table Figure m99Tc-MAA simulation indicated this as well (lower green area); the blue area is the area where predictive dosimetry failed to estimate a dose of more than 70 Gy, while the actual treatment reached that dose limit (n = 13); for eight tumors, pre-treatment simulation suggested a sufficient dose (more than 70 Gy) and post-treatment dose measurement revealed that the microsphere treatment did not meet this limit; the prediction was too optimistic here. Figure The same plot is provided in Fig. m99Tc-MAA uptake to distinguish between TV and NTV. Figure For 13 patients, the injected activity was prescribed by applying a compartmental partition model by thresholding For these 13 patients for whom the partition model was used for prescription, measured and predicted absorbed doses of 30 tumors were compared with TV planned dose. Figure m99Tc-MAA absorbed dose distribution is related to post-treatment microsphere dose distribution in the tumor, non-tumoral, and LPT compartments. The quantitative analysis showed that the correlation between m99Tc-MAA absorbed dose distribution is higher in the non-tumoral compartment than in the tumors. The non-tumor mean dose could be used in treatment planning to predict if the normal liver parenchyma receives a safe absorbed dose . In our analysis, we report a correlation between predicted and measured tumor absorbed dose employing a tumor-by-tumor approach instead of the patient averaged tumor dose. Analyzing the averaged predictive and measured tumor dose may lead to artefactual good correlation between pre- and post-therapy imaging. For example, Figs. m99Tc-MAA-based dosimetry could correctly predict if the dose to the tumor was sufficient or insufficient .This study presents a framework to compare predicted and measured absorbed doses for SIRT using CBCT-based VOI segmentation. To our knowledge, implementation of the contrast-enhanced CBCT in voxel-level dose comparison has previously not been studied. In other studies, either anatomical landmarks on non-catheter based anatomical imaging modalities  or activity uptake-based imaging modalities (PET or SPECT) were used to define LPTs corresponding to different catheter positions. We demonstrated that activity planning using m99Tc-MAA particles.Predicted absorbed dose estimation is becoming more and more crucial for individual SIRT planning . Bastiaam99Tc-MAA particles and 90Y-microspheres, as well as the inaccuracy in imaging and/or dose calculation and reporting techniques. Besides the difference in physical characteristics of two used radionuclides for dose prediction and measurement, a different catheter positioning and administration speed, vasospasm during one of the injection session, the embolic effect of the resin microspheres, and change in tumor vascularization between pre-treatment simulation and treatment session can lead to a weak predictive power of m99Tc-MAA particles. During the SIRT procedure, attempts were made to use the exact positioning of the catheter during the m99Tc-MAA injection and report any mismatching between the catheter tip position. In this study, clinical reports have been reviewed carefully for all screened procedures, and in case of a reported difference in catheterization, the case was excluded from the study.A disagreement between predicted and measured absorbed dose parameters can occur due to several factors , 21; it 90Y-TOF-PET imaging is considered to be quantitative with a limited margin of error. To avoid any systematic bias between the total activity (and absorbed dose) in the liver, the activity distribution of the post-treatment 90Y-PET image is rescaled based on the assumption that the total PET activity in the liver should equal the total prepared activity, considering no residual activity in vial nor catheters. On the other hand, the fractional uptake obtained from m99Tc-MAA-SPECT is rescaled assuming that the total predicted activity in each LPT should equal the administered activity within the corresponding catheter tip position.Calibrated activity in the vial is reported with an error of 20% , which cm99Tc-MAA solution, in vivo degradation products moving from the liver to the lungs, and scatter from the liver. This is substantiated by absence of uptake in the lungs according to 90Y-PET in all our patients.In both predictive and measured dose calculation, the LSF estimation based on planar imaging was not used at face value in the dose calculation as it overestimates the true lung shunt measurement . In our m99Tc-MAA-SPECT space and registered liver VOI in 90Y-PET space have been verified and modified by an expert. The ratio between liver volumes has a first, second, and third interquartile range of 0.99, 1.01, and 1.04, respectively. (b) For segmenting the liver perfusion territory corresponding to each catheter tip position, contrast-enhanced CBCT imaging is used. In our previous study, it has been shown that by aiming at delivering 40 Gy to the total liver and prescribing activity based on CT-based liver perfusion territories, absorbed dose to the right and left CBCT-based LPT has a median (range) of 40.8 Gy  and 38.1 Gy  [Lastly, any technical aspects of the VOI definition may alter the correspondence between predicted and measured dose parameters. To minimize this inaccuracy, additional control steps have been designed in this study: (a) liver segmentation by CNN in We found a strong correlation between non-tumoral liver mean dose, D30, and V40. Our results for mean tumor dose confirm the moderate correlation between predicted and measured tumor dose reported by Gnesin et al. . They alm99Tc-MAA absorbed dose estimation, Chiesa and Maccauro discussed the usefulness of extracting the correlation between predictive and post-therapy dosimetry parameters from a patient population to ”optimize treatment on the average” [Considering the reliability of average” . Indeed,m99Tc-MAA mean dose could predict either a safe activity planning or over-dosing of the healthy tissue . Also, for 69% of the tumors, m99Tc-MAA-based dose estimation could predict if the dose to the tumor was sufficient (more than 70 Gy).We adopted 70 Gy as the requirement for tumor response and 50 Gy as the safety threshold for non-tumor irradiation. Our results showed that for 97% of the patients, the m99Tc-MAA-SPECT or 18F-FDG-PET. Taking necrosis into account is more important for tumors with a high percentage of necrosis, typically large tumors. Our analysis suggests a median (first and third interquartile range) difference of 6%  and − 3%  between the projected and predicted mean dose for the non-tumoral and tumor compartments, respectively. It confirms that thresholding the m99Tc-MAA could result in an overestimation of the tumor dose prediction up to 50%. A more substantial discrepancy has been observed when comparing the planned dose and measured doses.We also compared predicted and measured absorbed doses to the projected (planned) absorbed dose. The planned absorbed dose has been calculated before treatment to prescribe activity based on the partition model. In this dosimetry scheme, activity thresholding is used to calculate tumor to normal activity concentration ratio. So, any inconsistency between planned absorbed dose and predicted absorbed dose reflects the effect of different applied VOI definition  solely. Notably, segmenting the tumoral lesion into different compartments (viable tumor and necrosis) is dependent on the imaging modality used. Here, we delineated the contrast-enhancing part of the tumor on CBCT (hypervascular areas) which could be different from tumor segmentation on MR or thresholding the m99Tc-MAA. In addition, detailed lesion analysis  could be performed in the future to refine tumor dosimetry.Several limitations could be mentioned for this study. First, the study design is retrospective. Also, the number of analyzed cases was limited; further studies, including more patients in homogeneous tumor types, are required to determine a better evaluation of the predictive value of m99Tc-MAA study is related to the post-treatment dose measurement. The agreement is stronger for non-tumoral liver parenchyma or total LPT than for the tumor compartment. Therefore, m99Tc-MAA-based activity planning using safety threshold could be used for SIRT planning before treatment to increase the tumor dose while avoiding overdosing of the normal liver parenchyma.In this study, we demonstrated that CBCT-based dose estimation using a Additional fileMore examples of pre- and post-treatment VOI segmentation and dosimetry.


N-ethanolamine triazine-piperizine, a melamine polymer (ETPMP), was established as a new charring-foaming agent and was successfully synthesized with ethanolamine, piperizine, cyanuric chloride, and melamine as precursor molecules via the nucleophilic substitution reaction method. Elemental analysis and Fourier transform infrared (FTIR) spectroscopy analysis were applied to approve the synthesis of ETPMP and confirmation of its structure and characterization. The epoxy coating of intumescent flame retardant (IFR) was equipped by introducing ETPMP, ammonium polyphosphate (APP), and copper oxide (CuO) in multiple composition ratios. CuO was loaded at various amounts into the IFR-coating system as a synergistic agent. The synergistic action of CuO on IFR coatings was scientifically examined by using different analytical tests such as vertical burning test (UL-94V), limited oxygen index (LOI), thermal gravimetric analysis (TGA), cone calorimeter, and scanning electron microscope (SEM). The results showed that small changes in the amount of CuO expressively amplified the LOI results and enhanced the V-0 ratings in the UL-94V test. The TGA data clearly demonstrate that the inclusion of CuO can transform the thermal deprivation behavior of coatings with a growing char slag proportion with elevated temperatures. Information from cone calorimeter data affirmed that CuO can decrease the burning factors by total heat release (THR) together with peak heat release rate (PHRR). The SEM images indicated that CuO can enrich the power and compression of the intumescent char that restricts the movement of heat and oxygen. Our results demonstrate a positive influence of CuO on the epoxy-headed intumescent flame retardant coatings.Epoxy resins (EP) have been used as a thermos-setting material in the field of coating, casting, bonding agent, and laminating. However, a major drawback associated with its use is the lack of good flaming properties, and it is responsible for heavy smoke along with hazardous gases considerably limiting its uses in various fields. In this study,  Epoxy resin (EP) has been used as a thermos-setting material in the fields of coating, casting, bonding agent, and laminating ,2,3. HowFire-resistant halogenated coatings are widely used, but these are associated with air pollution as they release hazardous gases. Therefore, an alternative non-halogen fire-resistant coating is the need of the hour. Two of the most commonly available non-halogen coatings are: (1) borate coatings and (2) magnesium/aluminum-controlled coatings. These coatings are effective fire-protectors as they form an opaque shielding char that minimizes the volume of fumes. On the contrary, these coatings mostly do not find practical applications because they are composed of heavy solids and their behavior in relation to binding agents is unclear . Thus, mThe intumescent flame retardant (IFR) technology having quality features as not releasing toxic gases on any burning conditions are widespread in current research scenario. Such coatings are very much popular and impactful while applied on the steel and wood materials. In general, the Fire retarded coating layers having three basic constituents as per their functionality that are as follows; (a) the acid source, (b) the foaming agent, and (c) the charring agent ,10. The To overcome such problems, researchers have made numerous attempts to produce materials that have both charring and foaming characteristics. In this context, the triazine molecule was selected to play a role as a charring-foaming producer with the ability to acquire a great quantity of carbon and nitrogen components ,14,15. MCopper oxide (CuO) is an inorganic crystal appearing as a red compound that is ecofriendly, having multiple catalytic applications and non-toxic on an industrial scale. Because of its acceptable catalytic properties, CuO is a remarkable substitute for metal catalysts ,25. BaseThis work is in the continuation of previous research based on fire retardant system examined . In curr−1 for N-H and O-H bonds-stretching patterns, respectively. The attributed peaks at 2944 cm−1 and 2883 cm−1 are for C-H bond-stretching interactions in the –CH2-CH2– group. The corresponding peaks at 1563 cm−1, 1407 cm−1, 1321 cm−1, and 1060 cm−1 are for νtr, δ O-H ν tr-N, and ν C-O, respectively. The peak at 850 cm−1 is absent in this spectrum, while one is specific for the C-Cl bond. Hence, we concluded that all three chlorine atoms of cyanuric chloride are successfully involved in this substitution. Our result is in accordance with a study demonstrating similar FTIR spectra for ETPMP [or ETPMP .The ETPMP polymer elemental composition data is tabulated in TGA data provide information about the thermal stability of a polymer. The UL-94V test data of the samples show that, except for pure coating, all of the samples meet V-0 (high flame retardant) ratings. From LOI and UL-94V results, it became clear that incorporation of CuO can significantly enhance the flame retardant activity until its optimum loading concentration.The thermal stability of pure epoxy resin, Ep/IFR, and Ep/IFR/CuO-5% are represented in The combustion behavior of the polymers and materials was evaluated by the widely used cone calorimeter. −2. The epoxy coating ignited at 347 s. The Ep/IFR and Ep/IFR/CuO-5% coatings have PHRR values of 397.8 and 294.8, respectively. This means the PHRR values are greatly reduced from 100% to 57.36% and 42.50% for Ep/IFR and Ep/IFR/CuO-5% coatings, respectively. A TTI (Time to Ignition) value provides information on the ignition parameter. The Ep/IFR and Ep/IFR/CuO-5% have lower TTI values than pure epoxy. The results show that the ignition values for Ep/IFR and Ep/IFR/CuO-5% are decreased from 347 s to 279 s and 265 s, respectively. −2, whereas the compositions of Ep/IFR and Ep/IFR/CuO-5% coatings showed a significant decrease in THR value from 112 to 73 and 42 MJ m−2 kg, respectively. The THR values of Ep/IFR and Ep/IFR/CuO-5% coatings were 34.83% and 62.5% lower, respectively, than epoxy coatings. The THR  data of the epoxy, Ep/IFR, and Ep/IFR/CuO-5% coatings are shown in During the combustion process, the IFR system forms a char with foam. The loading of CuO into the coating system can speed up the intumescent reaction to form a compact char. The resulting char acts as a strict barrier for the oxygen and flow of heat, greatly reducing PHRR and THR values. Among all the coatings samples, the Ep/IFR/CuO-5% coating showed the lowest PHRR, THR, and TTI values. As CuO helps in the homogenous and compact char formation, the CuO-loaded coating samples showed good combustion behavior. The results prove that CuO can be used as a synergist.The char residues of Ep/IFR and Ep/IFR/CuO-5% obtained in the combustion test were imaged by SEM with 500× and 3000× magnification. The SEM pictures of Ep/IFR and Ep/IFR/CuO-5% charred layers are shown in Bisphenol A (≥99%), an epoxy resin was supplied from Sigma-Aldrich . Polyamide was obtained from Sigma-Aldrich  and was utilized as a curing agent for epoxy resin. The commercial ammonium polyphosphate  was purchased by Samchun Company, Seoul, Korea. The solvents ethanolamine (99%), ethanol (98%), and acetone (99.5%) were bought from Sigma-Aldrich . The chemicals cyanuric chloride (99%), melamine (99%), piperizine (99%), copper oxide , and sodium hydroxide (NaOH) pellets were supplied by Sigma-Aldrich . All chemicals were used as received without any further modification. N-ethanolamine triazine-piperizine, a melamine polymer (ETPMP), was synthesized by a three-step nucleophilic substitution reaction as described previously [The charring-foaming agent eviously . The synIn step 1, 1 L of acetone and 1 mole of cyanuric chloride were transferred into a dry, clean, three-necked round-bottom flask with a 3 L capacity, and the reaction was maintained at 10 °C. One mole each of ethanolamine and NaOH were thoroughly liquefied in 1 L of distilled water in a separate flask, and the solution was transferred to the three-necked round bottom flask with continuous stirring for 2 h. At this point, the first step was complete and provided us with 2-ethanolamine-4, 6-dichloride-1, 3, 5-triazine as intermediate compounds. The remaining intermediate compounds were left in the three-necked round-bottom flask. Step 2 began with the complete dissolution of 0.5 moles of piperizine and 1 mole NaOH in 1 L of water in a separate flask, and this mixture of solutions was slowly transferred into the three-necked flask and left for 2 h. Next, the temperature was raised and maintained between 45 and 50 °C with continuous stirring for the next 4 h. In the third and last stage of the synthesis, 1 mol of NaOH and 0.3 moles of melamine were fully dissolved in 1 L of water in a separate flask. The solution was transferred into a three-necked reaction bottle. Next, the temperature of the reaction was increased again up to 70 °C for the exclusion of acetone. The step was implemented for the next 6 h to finish the reaction. The precipitate obtained was white in color and was filtered and washed thrice by ethanol to removes contamination from the final proposed product of ETPMP. Finally, 194.6 g white powder was obtained.APP and ETPMP, at a 2:1 proportion, were mixed with CuO (synergist) and added into epoxy resin (2:1) to prepare the IFR coating. CuO with APP, ETPMP were mixed in epoxy resin and dispensed into a dispersion blender for uniform mixing. Next, the prepared coatings material was brushed on selected plywood fragments for further examination and characterization. The pieces of plywood were left for two days in a ventilated room to dry completely. The composition details of the coating are listed in −1 condition. We monitored the samples in a 4000–400 cm−1 range for structural information. A Nicolet Avator 360 FT-IR spectrometer instrument  was employed to enroll the spectra of the samples at 2 cmA Carlo Erba 1110 instrument  was employed to check ETPMP polymer elemental composition. The obtained data are listed in The LOI tests for the samples were conducted on HC-2C Oxygen Index instrument . For this test, we applied 10 g of each coating compositions on plywood sheets with 130 × 6.5 × 3 mm dimensions.A CZF-2 instrument  was used to record the UL-94V rankings of the testing samples. The prepared coatings were applied on 130 × 13 × 3.2 mm sized plywood pieces and dried. The results obtained are presented in A SDT Q600 V20.9 Building 20 instrument  was used to check the thermal stability of the samples. The conditions of this test were 30 to 800 °C with 10 °C/min and 20 mL/min flow rate of nitrogen gas. To conduct this test, we took each sample at 5–10 mg weight.−2 of external heat flux.All combustion data were taken from the cone-calorimeter instrument  that was used to perform the combustion test of all samples. The samples were placed horizontally on the sample holder. The sample was exposed to 35 kW mA scanning electron microscope JSM-6360  was employed to analyze the morphological differences of the char layers. A gold layer was deposited on the char surface for the sputtering process. An acceleration voltage of 15 kV was maintained during the experiment. We performed this test using an HY-0230 machine . For this test, we kept char on a circular platform, slightly increased the pressure on the char layer, and recorded where the char layer was damaged.N-ethanolamine triazine-piperizine, a melamine polymer (ETPMP), was prepared successfully. FTIR and elemental analysis data support its structural confirmation. Various IFR-Epoxy-CuO coating formulations were prepared. The loading of a small quantity of CuO into the Ep/IFR coating system can effectively increase the LOI value and reach UL-94V rankings. The LOI and UL-94V data show that the optimum amount of CuO is 5%. The TGA study showed that CuO can improve the thermal stability and char residue percentage of the samples at high temperatures. Cone calorimeter data confirm that CuO can effectively decrease the heat-releasing property. The SEM and strength analysis data prove that adding CuO at a suitable dosage can greatly encourage the formation of a uniform and compact charred layer in the burning environment of this coating. In conclusion, CuO exerts a positive influence on the epoxy headed intumescent flame retardant coatings. It is envisaged that the ecofriendly and non-toxic Copper Oxide on epoxy coatings could be exploited to develop a fire-retardant coating for the protection of inflammable materials.A new triazine derivative polymer


What is the overall concordance between FRIED-P and FRIED-Q?The concordance between the FRIED-P and FRIED-Q was substantial, characterized by a very high specificity but a moderate sensitivity.The FRIED-Q can be used as a step in a sequential process to detect frailty in a large population.The online version of this article (10.1007/s41999-020-00337-8) contains supplementary material, which is available to authorized users. When screening large populations, performance-based measures can be difficult to conduct because they are time consuming and costly, and require well-trained assessors. The aim of the present study is to validate a set of questions replacing the performance-based measures slowness and weakness as part of the Fried frailty phenotype (FRIED-P).A cross-sectional study was conducted among community-dwelling older adults (≥ 60 years) in three Flemish municipalities. The Fried Phenotype (FRIED-P) was used to measure physical frailty. The two performance-based measures of the Fried Phenotype (slowness and weakness) were also measured by means of six substituting questions (FRIED-Q). These questions were validated through sensitivity, specificity, Cohen’s kappa value, observed agreement, correlation analysis, and the area under the curve .r = 0.721 with an observed agreement of 76.6% .196 older adults participated. According to the FRIED-P, 19.5% of them were frail, 56.9% were pre-frail and 23.6% were non-frail. For slowness, the observed sensitivity was 47.0%, the specificity was 96.5% and the AUC was 0.717. For weakness, the sensitivity was 46.2%, the specificity was 83.7%, and the AUC was 0.649. The overall Spearman correlation between the FRIED-P and the FRIED-Q was The concordance between the FRIED-P and FRIED-Q was substantial, characterized by a very high specificity, but a moderate sensitivity. This alternative operationalization of the Fried Phenotype—i.e., including six replacement questions instead of two performance-based tests—can be considered to apply as screening tool to screen physical frailty in large populations.The online version of this article (10.1007/s41999-020-00337-8) contains supplementary material, which is available to authorized users. Physical frailty is a state of increased vulnerability, which can evolve into disability and other adverse outcomes –5. HowevNonetheless, a recent study did test the psychometric properties of six self-report questions to replace the performance-based measurements slowness and weakness . In thisWhereby the study of Op het Veld and colleagues was explorative, the aim of the present study is to validate and to confirm the psychometric properties of this set of six self-report questions . HoweverThe research questions of the present study are: (1) What is the concordance between slowness operationalized by doing a 15 ft. walk time test and slowness operationalized by four self-report questions? (2) What is the concordance between weakness measured by means of a handgrip strength test and weakness operationalized by two self-report questions? (3) What is the concordance between the two overall operationalization’s of the Fried scales? (4) What is the ability of the Fried Phenotype with no performance-based tests to discriminate between non-frail and/or frail older adults if we take the Fried Phenotype with performance-based test as a gold standard?p < 0.05) by means of a correlation of 0.30. Participants had to be community dwelling and 60 years or older and were selected from the census records, based on risk profiles  developed by Dury and colleagues [For this cross-sectional study, data were gathered as baseline wave within the D-SCOPE project . D-SCOPElleagues , 18. ParFried’s Phenotype of physical frailty was used to measure frailty . The FriTo describe the population, univariate descriptive statistics were conducted. To get an impression whether the items of slowness and the items weakness are related, the mean inter-item correlations were calculated for both measurements. A low inter-item correlation suggests that the items are hardly related to each other and might not be suitable for measuring a single construct. A high inter-item correlation suggests that the items tend to be very similar to each other, almost to the point that they are redundant. Optimal mean inter-item correlation values range from 0.2 to 0.4 .In research questions 1 and 2, we examine the concordance between the performance-based test  and the replacement questions, to have a better understanding of the concordance if several tests were applied: sensitivity, specificity, observed agreement, Cohen’s kappa (interrater reliability); the performance of the model for both hand grip strength and walk time was quantified as the area under the receiver operating characteristic curve (AUC) –22.To measure the AUC, the scores on the replacement question of hand grip strength and walk time were used as test variable and the score on the performance-based test was used as state variable.To measure the concordance between the FRIED-P and the FRIED-Q (research question 3), the Spearman correlation and observed agreement were computed. Since the Fried Phenotype has three categories, frail, pre-frail and non-frail, a weighted kappa value (linear and quadratic) was calculated, whereby the FRIED-P was used as the ‘gold standard’.To measure the ability of the FRIED-Q to discriminate between non-frail and/or frail people (research question 4), the sensitivity, specificity, Cohen’s kappa, observed agreement and area under the receiver operating characteristic curve (AUC) were measured against the FRIED-P.The interpretation of the (Cohen’s) kappa value was divided as follows: < 0: poor; 0–0.20: slight; 0.21–0.40: fair; 0.41–0.60: moderate; 0.61–0.80: substantial; 0.81–1.00: almost perfect . The areIn total, 196 participants participated in the study with an average age of 72.7 (SD 8.0) of which 49.0% was male. The characteristics of the population are further described in Table According to the FRIED-P, 19.5% of the population was frail, 56.9% was pre-frail, and 23.6% was non-frail (not tabulated). According to the FRIED-Q 14.6% was frail, 52.1% was pre-frail, and 33.3% was non-frail (not tabulated). For the four questions related to slowness, the mean inter-item correlation was 0.266, which is between the range of the optimal inter-item correlation. The mean inter-item correlation value for weakness was 0.221, which is also between the range of the optimal inter-item correlation.κ = 0.464, and was defined as moderate.The AUC for slowness was 0.717, which can be defined as fair. The replacement questions for slowness had a sensitivity of 47.0% and a specificity of 96.5% . The Spearman correlation between the FRIED-P and FRIED-Q (5 items) was r = 0.721.The observed agreement of the three frailty stages between FRIED-P and FRIED-Q was 76.6%. The kappa value was substantial (unweighted κ = 0.686).When distinguishing between frail and non-frail/pre-frail older adults, the FRIED-Q had a sensitivity of 64.9% and a specificity of 97.4% against the FRIED-P Table . The obsκ = 0.647).When distinguishing between non-frail and frail/pre-frail older adults, the FRIED-Q had a sensitivity of 84.2% and a specificity of 89.1% against FRIED-P  and FRIED-Q (including self-report questions for slowness and weakness) was substantial. The FRIED-Q is very well in discriminating physically non-frail older adults (specificity 89.1%), but somewhat less in discriminating frail older adults (sensitivity 64.9%). At an item level, slowness and weakness are characterized by a low sensitivity , but high specificity .The observed agreement (76.6% versus 71.1%) and Cohen’s kappa value (0.607 versus 0.55) of the total scales (research question 3) are slightly better in comparison with the results of Op het Veld et al. . HoweverThe concordance between the Fried Phenotype performance-based measures (slowness and weakness) and the set of replacement questions at item level is fair. In previous studies, discrepancies between self-report measures and performance-based tests were found. For instance, the results in a prior systematic review indicated a correlation range between 0.60 and 0.86 when the same construct was measured in two different ways . As far When distinguishing between non-frail older adults and frail older adults, the total FRIED-Q was marked by a high specificity (89.1%), but a rather low sensitivity (64.9%). This indicates that people might overestimate their own physical performance while filling in the FRIED-Q. For instance, 44 participants reported no slowness (FRIED-Q), while according to the walk time test they were. On the other hand, only a small number of people (four participants) underestimated their own walk speed (slowness). Previous research found several confounding factors for overestimating own physical competences, such as perceived physical competence, perceived health status, personal control or mastery, and depressive symptomatology –30. For In the present study, the prevalence is higher than in comparison with previous research. There are several plausible reasons which can explain why the prevalence of frailty is higher: (1) in the present study, older adults were selected from the census records based on risk factors for frailty. Therefore, the prevalence of frailty will be higher and not representative for the population; (2) differences in inclusion and exclusion criteria, for instance, in the SHARE survey, the sample was aged 50 years and over, while in the D-SCOPE project people had to be 60 years or older ; (3) a pThis study has several strengths and limitations. A strength of the present study is that it replicates the study of Op het Veld and colleagues in a larger sample, whereby it was performed in a different setting and region (Flemish region in Belgium) . ConsequThe substantial concordance between the FRIED-P and the FRIED-Q suggests the usefulness of the latter to screen frailty in a large population, since the FRIED-Q is easier to apply in comparison with the FRIED-P. The high specificity is an advantage when the objective is to exclude non-frail persons, for instance in (research) projects where being frail is often an inclusion criterion). However, the FRIED-Q does not detect all frail older adults (according the Fried Phenotype) and can be considered as a step in a sequential process to detect frailty in large populations. This sequential process should reduce the number of false positives and false negatives. For instance, most older adults (aged 75 and over) in Europe consult their GP frequently. If large screening of frailty becomes a responsibility of general practitioners, there are frequently occasions to screen the patient. In case of doubt the performance-based tests can still be applied as a second order. Future research is needed to validate these sets of substitution questions in other languages and settings.Supplementary file1 (DOCX 30 kb)Supplementary file2 (DOCX 208 kb)Supplementary file3 (DOCX 14 kb)Supplementary file4 (DOCX 20 kb)Below is the link to the electronic supplementary material.


Suchana—a large-scale, 7-year nutrition program that started in 2015—is being implemented in 250,000 households in the marginalized segment in north-east Bangladesh, with the aim of improving childhood nutrition status. Untreated childhood moderate wasting may develop to severe wasting, which is associated with a 10-fold higher risk of mortality compared to children of normal weight relative to height/length. Identifying the diverse, age-specific risk factors for moderate wasting may help such programs to formulate tailored interventions to prevent and treat childhood malnutrition in rural communities. The objective of this study was to identify the age-specific factors associated with moderate wasting among 6‒23-month-old children in beneficiary households. Cross-sectional data on 4,400 children was collected through systematic sampling between November 2016 and February 2017 using the Suchana beneficiary list. In total, 8.1% of 6‒11 month-olds and 10.3% of 12‒23 month-olds suffered moderate wasting; 12‒23-month-olds had a 1.3-fold higher risk of moderate wasting than 6‒11-month-olds. Our results of logistic regression models suggest that larger household size, higher maternal body mass index (BMI), and maternal food consumption status more than usual during the recent pregnancy were associated with a reduced risk of moderate wasting among 6‒11-month-olds. Higher maternal BMI, normal maternal food consumption status during last pregnancy, being female and maternal knowledge on diarrheal management, were associated with a reduced risk of moderate wasting among 12‒23-month-olds. In conclusion, beyond maternal BMI and maternal food consumption status during the last pregnancy, the factors associated with moderate wasting among 6‒23-month-olds in the poorest households in Bangladesh are age-specific. Globally, around 238 million children under five years-of-age are either undernourished or overweight . UndernuAcute malnutrition is characterized by excess loss of body weight for height/length (wasting), low mid-upper arm or nutritional edema . Acute mIn Southern Asia alone, if both WHZ-score and MUAC cut-offs are considered, 25.3 million under-fives suffer wasting, of whom 64% have moderate wasting  and 8.7 The recent Demographic and Health Survey in Bangladesh revealed that around 14% children under-five were wasted, with the prevalence reaching 20% for 9‒11-month-olds , indicatPromoting and supporting breastfeeding, counseling on complementary feeding practices, energy-and nutrient-dense food supplementation and improving dietary diversity and quantity for older children are recommended to both prevention and treatment of MAM in the community , 14, 15.Suchana is a large-scale, 7-year nutrition program serving around 250,000 poor households with the highest vulnerability to malnutrition in north-east Bangladesh; the program began in 2015 and will reach around 1.7 million people in the Sylhet and Moulvibazar districts . Sylhet The aim of this study is to identify the age-specific factors associated with the occurrence of moderate wasting among Suchana beneficiary children. In this study we have defined moderate wasting as the WHO cut-off of a WLZ-score of between– 2 to -3 and did not include cases as per MUAC cut-off values or observation of nutritional edema. This information may help the Suchana program and other large-scale nutrition programs with similar priorities to effectively divert and mobilize the necessary resources towards the root causes or domains that influence moderate wasting and inform the development of effective strategies to prevent malnutrition among children in poor households.This study was approved by the Research Review Committee and Ethical Review Committee, the two obligatory components of the institutional review board of International Centre for Diarrhoeal Disease Research, Bangladesh  under research protocol number PR-16020. Informed written consent was obtained from the parents of all children. The respondents were also informed that their participation was voluntary and of their right to withdraw themselves from the study at any point for any reason. Information that could reveal any respondent’s identity was not used while analyzing the data. The Suchana evaluation study has been registered at the Registry for International Development Impact Evaluations (RIDIE) as RIDIE-STUDY-ID-5d5678361809b.Cross-sectional data on 4,400 children aged 6‒23 months, including 1,200 children aged 6‒11 months and 3,200 aged 12‒23 months, was collected through the Suchana baseline survey using a structured questionnaire and anthropometric measurements.The minimum sample size required to achieve 80% power and a 5% level of significance was determined using the proportion of 6‒11-month-olds in the Sylhet region who consumed four or more food groups (minimum acceptable diet) in the 24 hours preceding the survey . The proportion of MAD used for calculation was 24.6% with an intra-cluster correlation (ICC) of 0.0395 .clustersampsi module.The minimum sample size required for the 12‒23-month-old group was based on the prevalence of stunting from the same unpublished study and an assumed difference of 6% between the intervention and control groups after three years of the intervention: we expected the prevalence of stunting in the control group to be around 47% at the end of the first 3 years of the Suchana program . The minimum sample size required to detect a 6% difference in the prevalence of stunting between groups was calculated assuming 80% power, 5% significance and an ICC of 0.01 . The sample size calculations were conducted in Stata software (STATA Corp.) using the The Suchana baseline survey was conducted between November 2016 and February 2017 in 80 unions  of the Sylhet and Moulvibazar districts. Eighty unions (containing 640 villages) were selected from the unions in the two districts using a lottery method. Vulnerable villages in each of the selected unions were identified through consultation with local elites, such as local teachers, local administrators, religious leaders, local non-government and government authorities, and local political leaders. Depending on the population of each village, one or two wealth ranking sessions were conducted in each village following a participatory rural appraisal strategy , in whicHouseholds in which (i) the members of the household could not have three full meals a day throughout the year; (ii) the monthly household income was less than Tk. 7500 (1 USD = ~ Tk. 82); (iii) with total household business assets worth less than Tk. 15,000 ; (iv) with less than 10 decimals of homestead land or (v) with less than 50 decimals of cultivable land  were eligible for enrollment if any one of the following conditions was satisfied: (i) the household has a married women between 15 to 45-years-old; (ii) the household has a pregnant woman (including divorcees and widows); (iii) the household has at least one child under two-years-old or at least one female adolescent aged between 15 and 19-years-old. However, households in which the beneficiary was pregnant were excluded from the sampling list for the evaluation as reported data on estimated maternal body mass index (BMI) would be inaccurate or overestimated. Households were selected for the baseline survey using a systematic sampling strategy by calculating an ‘interval’ using the total number of eligible potential beneficiary households available and the minimum sample size required. The calculated interval for selecting households was 1.89, with the first household chosen randomly from the household list. Informed written consent was obtained from the mothers of the children after the purpose of the survey was clearly explained to them in Bengali language and a copy of the consent form was provided to the participants for future reference.Data were collected using Personal Digital Assistants (PDAs) by field staff members after completion of three months’ training on administering the questionnaire and anthropometry  team randomly re-visited 5% of the surveyed households and re-examined 25 key indicators from the original survey. Immediate feedback was provided to the survey team if any discrepancies were found. During the survey, all data collectors checked the collected data on-site and uploaded the data after the responses had been scrutinized by field supervisors.The data management team downloaded the data from the server, performed range, duplication, consistency and frequency checks and conducted cross-tabulation. If any inconsistencies were found, the field supervisors were immediately informed and took rectifying steps. The downloaded data was stored in a password-protected personal computer in a specific drive or folder that could only be accessed by selected investigators. After a specific time period, all data was backed up on three storage instruments: another drive and folder on the same computer, the principal investigator’s computer, and an external password-protected hard drive placed in both secure location and a secure building.The outcome variable was the occurrence of moderate wasting, as defined by the WHO as a cut-off of weight-for-length z-score (WLZ) between -3 and -2. A WLZ-score below -3 was considered severe wasting . The varsvyset command was used to adjust for the clustering effect during bi-variate and multivariable analyses. Simple logistic regression and multiple logistic regression were used to illustrate the crude and independent relationships between the variables of interest and moderate wasting among the children by age groups (6–11 months and 12–23 months). p-values less than 0.05 were considered statistically significant.All statistical tests were performed in Stata 15 software. The z-scores were calculated using the ZSCORE06 package of Stata 15 . Descripp-value < 0.05 were used in the conventional final multiple logistic regression models. Several post-estimation diagnostics such as collinearity diagnostics (collin), the Pearson or Hosmer-Lemeshow goodness-of-fit test (lfit), classification statistics and table (lstat) and the specification link test for single-equation models (linktest) were subsequently performed to test for multicollinearity between variables and assess the overall model fit and overall predictive accuracy of the models.All variables in the bi-variate analyses with a All variables in the final regression method were entered simultaneously according to the ‘ENTER’ method for logistic regression. The final regression model for the 6‒11-month-old group included household size, maternal BMI, maternal food consumption status during last pregnancy, maternal knowledge on consequences of early pregnancy, maternal knowledge on attending at least four antenatal appointments, and whether the child received colostrum as independent variables. The final regression model for the 12‒23-month-old group included household savings status, asset index, maternal BMI, maternal education status, type of antenatal care provider, maternal food consumption status during last pregnancy, maternal knowledge of health care providers, maternal knowledge on exclusive breastfeeding, maternal knowledge on diarrheal management, and the gender of the index child as independent variables. The data analysts were blinded to the identity of the participants .Data was available for 4,400 children and households in the population targeted by the Suchana program. The descriptive results indicated that 8.1% and 10.3% of children in the 6‒11 and 12‒23-month-old groups suffered moderate wasting, with respective mean weight-for-length z-scores of -2.35 ± 0.28and -2.37 ± 0.26. The difference in proportion of moderate wasting and overall mean WLZ-scores between the age groups were statistically significant (p<0.05). Moreover, 1.57% of 6‒23-month‒olds were suffering SAM, with a mean WLZ-score of -3.73 ± 0.87 (Data not shown).Among the sampled children, 51% were male and 22.9% and 20.3% of 6‒11 and 12‒23-month-olds were the first child of their parents. In total, significantly more children (p < 0.001) among the 6–11 month- had suffered morbidity within 15 days preceding the survey (56.3% vs 50.4%). In terms of child feeding practices, 85.3% and 83.7% of 6‒11 and 12‒23-month-olds had received colostrum after birth and 87.4% and 86.7% had initiated breastfeeding within one hour after birth. Additionally, 5.8% and 11.9% of children received a minimum acceptable diet (MAD), a critical indicator of feeding practices for young children, in the 6‒11 and 12‒23-month-old groups and the difference in proportion between the groups was statistically significant (p<0.001).The mean household size was 6.31 ± 2.39 and 6.24 ± 2.37 and median household annual income was Tk. 80,000  and Tk. 80,000  for the 6‒11 and 12‒23-month-old groups, respectively. Furthermore, 31.9% and 33.8% of spouses had savings and 13.9% and 14.0% of households with 6‒11 and 12‒23-month-olds were food secure.2 for both the groups. Among the mothers of the 6‒11 and 12‒23-month-olds, 56.3% and 53.1% washed hands at least during the three critical times.The mean maternal age was 26.52 ± 5.72 and 27.46 ± 5.66 years for the 6‒11 and 12‒23-month-old groups and was statistically significant (p<0.001) and mean BMI was around 19.6 kg/mIn terms of maternal reproductive characteristics, 42.8% and 40.4% of mothers in the 6‒11 and 12‒23-month-old groups had received iron and folic acid (IFA) supplementation during their last pregnancy, 15.6% and 14.3% had attended at least four antenatal care (ANC) checkups, 59.8% and 56.3% had visited appropriate institutions for ANC, and 62.8% and 57.8% received ANC from qualified providers. The mean number of maternal pregnancies was 3.23 ± 2.12and 3.27 ± 2.11 for the 6‒11 and 12‒23-month-old groups. Overall, 26.1% and 25.4% of mothers in the 6‒11 and 12‒23-month-old groups reported consuming more than usual or additional food and 33.8% and 35.8% reported resting more than usual during their last pregnancy.With respect to maternal knowledge, 81.5% and 81.2% of mothers in the 6‒11 and 12‒23-month-old groups knew the importance of IFA supplementation during pregnancy and 82.0% and 83.4% were aware of the importance of children consuming Vitamin A capsules, 43.4% and 45.8% could mention at least one adverse consequence of early pregnancy, 36.8% and 36.0% knew the minimal number of ANC visits required during pregnancy, and 76.3% and 75.9% of mothers identified appropriate health care providers in the community. Additionally, 93.1% and 92.9% knew the importance of initiating of breastfeeding within one hour of birth, 62.8% and 59.6% knew about the importance of exclusive breastfeeding, and 5.3% and 6.1% could describe appropriate diarrheal management for children. The descriptive results of the age groups are presented in p < 0.05; data not shown].Simple logistic regression models by age showed that children aged 12‒23 months had a 1.3-fold higher risk of moderate wasting compared to 6‒11-month-olds . Higher maternal BMI  and maternal consumption of more food than usual during the last pregnancy  were associated with a lower risk of moderate wasting in the 6‒11-month-old group.Simple and multiple logistic regression analyses of all children and the children by their age groups are summarized in p < 0.001; aOR: 0.93 (95% CI: 0.89–0.98), p < 0.01], consumption of a normal amount of food during the last pregnancy , and having maternal knowledge of diarrheal management  were associated with a significantly lower risk of moderate wasting among 12‒23-month-olds. Being female  was associated with a significantly lower risk of moderate wasting among 12‒23-month-olds. The results are shown in Higher maternal BMI [OR: 0.91 (95% CI: 0.87–0.96); In respect of the post-diagnostic tests, all variables used in the multiple regression models for the 6‒11-month and 12‒23-month-old groups had VIF of around 1.0 (mean VIF: 1.05 and 1.06), suggestive of minimum multicollinearity. The overall predictive accuracy was 91.9% for the 6‒11-month-old group regression model and 89.7% for the 12‒23-month-old group, indicating good predictive accuracy of models as well as absence of significant multicollinearity. When considering all children, the asset index, maternal BMI, maternal food consumption status during last pregnancy, maternal knowledge of diarrheal management, the gender of the index child, and consumption of any medicine or vitamin drops by child on the previous day were statistically significant factors associated with moderate wasting. The trial profiles for the two age groups are presented in Figs The purpose of this study was to identify the factors associated with the occurrence of moderate wasting among children under two-years-old in the Suchana program catchment households in rural Bangladesh.Positive associations between increased maternal food consumption during pregnancy and adequate pregnancy weight gain with birth outcomes and subsequent growth and development and association between maternal nutrition during pregnancy and fetal growth have been documented in the literature , 30. FetAdditionally, we have found that higher maternal BMI was significantly associated with moderate wasting in both the age groups, as previously observed in several studies in Bangladesh , 32–34. Over 8% of 6‒11-month-olds and 10% of 12‒23-month-olds were suffering from moderate wasting among the studied marginalized population, which is similar to the contemporary prevalence of moderate wasting among Bangladeshi under-fives of around 14% among the general population , 19. HowChildren aged 12‒23 months were significantly more likely to suffer moderate wasting than 6‒11-month-olds, in confirmation of similar findings that older age was significantly associated with moderate wasting in children . HoweverPrevious literature found that children’s nutrition status is associated with food availability in the household . Larger Our analyses involving wasting were based on the WHO suggested cut-off values using weight-for-length z-score. The literature suggests that while both diagnose wasting, MUAC and WLZ-score are both independent indicators: MUAC is primarily used as a screening tool at the community level and WLZ-score is used in health care facilities. There is a poor correlation between MUAC and WLZ-score, calculations have shown that cut-off values for detecting moderate wasting using MUAC perform poorly compared to the same populations defined by WLZ-score .An analysis of the cost-effectiveness of interventions for maternal and child health outcomes in terms of cost per death averted showed that maintaining optimal nutrition during pregnancy was the most expensive intervention . NonetheMultiple studies , 45, 46 Gender emerged as a significant factor associated fwith moderate wasting: male children in the older age group were significantly more vulnerable than females. Though similar findings on wasting and undernutrition have been repeatedly documented by similar studies , 42, 48,The infection-malnutrition cycle  suggestsNational guidelines have been published for the community management of moderate wasting in Bangladesh  and actiThe relationship between seasonality in Bangladesh and the occurrence of moderate wasting was not examined in this study; nonetheless, the occurrence of moderate wasting does not have a peak season in Bangladesh. We have only analyzed cases confirmed to have acute malnutrition as defined by the WLZ-score cut-off value, inclusion of cases defined as acutely malnourished by MUAC cut-off value, may have given us the opportunity to analyze the full spectrum of cases that can be considered as moderate acute malnutrition. The recall period for acute morbidity was only 15 days, thus this variable does not indicate the duration of the morbidity episodes. Causality cannot be inferred due to the cross-sectional nature of this study; hence, only association between variables were reported. The Suchana program included marginalized households only, thus the inferences derived from this study was applicable to the marginalized sup-group and may not necessarily represent determinant factors among the general population of Bangladesh. Finally, information collected through maternal responses may be prone to recall bias. Nonetheless, the systematic sampling and robust sample size ensured that potential recall bias is diluted.This study was approved by the Research Review Committee and Ethical Review Committee, the two obligatory components of the institutional review board of International Centre for Diarrhoeal Disease Research, Bangladesh  under research protocol number PR-16020. Informed written consent was obtained from the parents of all children. The respondents were also informed that their participation was voluntary and of their right to withdraw themselves from the study at any point for any reason. Information that could reveal any respondent’s identity was not used while analyzing the data. The Suchana evaluation study has been registered at the Registry for International Development Impact Evaluations (RIDIE) as RIDIE-STUDY-ID-5d5678361809b.S1 File(DOCX)Click here for additional data file.S1 Data(XLS)Click here for additional data file.